CD8+ T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis
CD8+ T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis
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DOI：
10.1172/jci9295
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发表时间：
2000-07-01
影响因子：
15.9
通讯作者：
Sorrentino, R
中科院分区：
文献类型：
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作者：
Fiorillo, MT;Maragno, M;Sorrentino, R
HLA-B27与强直性脊柱炎（AS）高度相关，但其机制尚不清楚。在HLA-B27等位基因中，B*2709与易感的B*2705相差一个氨基酸，与该疾病无关。在此，我们分析了AS患者和携带B*2709或B*2705等位基因的健康对照对来源于LMP 2的EBV表位（236-244）和来源于血管活性肠肽受体1的序列相关自身肽（VIP 1 R 400 -408）的反应性。我们发现，B*2705（+）和B*2709（+）受试者都具有LMP 2 236-244特异性、HLA-B27限制性T细胞，而只有B*2705（+）个体对VIP 1 R 400-408有显著应答。这些结果促使我们通过IFN-γ ELISPOT分析比较AS患者与B*2705健康对照者对VIP 1 R 400-408的T细胞应答。数据显示VIP 1 R 400-408特异性反应性是AS患者的主要特征。这些研究结果表明，第一次，我们的知识，广泛的反应性AS患者对自身抗原决定簇，表现出一些功能的推定的“关节炎”肽。
HLA-B27 is highly associated with ankylosing spondylitis (AS), but the mechanism is unknown. Among the HLA-B27 alleles, B*2709, which differs by one amino acid from the susceptible B*2705, is not associated with the disease. Here, we analyze the reactivity, in patients with AS and in healthy controls carrying the B*2709 or B*2705 alleles, to an EBV epitope derived from LMP2 (236-244) and to a sequence-related self-peptide from vasoactive intestinal peptide receptor 1 (VIP1R400-408). We found that both B*2705(+) and B*2709(+) subjects possess LMP2 236-244-specific, HLA-B27-restricted T cells, whereas only the B*2705(+) individuals respond significantly to VIP1R 400-408. These results prompted us to compare, by IFN-gamma ELISPOT analysis, the T-cell response to VIP1R 400-408 in patients with AS versus B*2705 healthy controls. The data show that VIP1R 400-408-specific reactivity is a major feature of the patients with AS. These findings show, for the first time to our knowledge, a widespread reactivity in patients with AS against a self-epitope that exhibits some features of a putative "arthritogenic" peptide.